We will continue development of a novel optical probe for non-invasive characterization and monitoring of the biochemical and morphological changes in oral cavity epithelium leading to dysplasia and ultimately to invasive squamous cell carcinoma. Oral squamous cell carcinoma is a pathological condition that kills approximately half of patients afflicted within five years of diagnosis and may leave surviving patients with severe aesthetic and/or functional compromises. Early detection of oral precancerous lesions can have a dramatic impact on oral cancer mortality rates, increasing survival rates from 50% to about 80%. Current methods of oral cancer screening include visual assessment enhanced by application of acetic acid solution or stains such as toluidine blue or Lugol iodine. Definitive assessment is by invasive excisional biopsy. Visual assessment suffers from a wide variability in perception between clinicians and is unable to detect extremely early signs of neoplastic transformation. Biopsy can only be used sparingly. In this proposal we will combine the power of tissue autofluorescence imaging, (which is highly sensitive to biochemical changes associated with very early neoplastic transformation) with optical coherence tomography (which provides detailed sub-surface morphological information.) By combining these two modalities, we can leverage the speed and sensitivity of fluorescence imaging to direct the highly specific application of OCT imaging. In this way we produce an instrument which can be used for rapid and definitive screening or diagnosis of oral pathology. We will characterize the utility of the instrument in a study of 80 patients in the UTMB ENT clinic. Finally, while we have focused this application on oral cancer, the FIG-OCT system will have wide application in a number of other tissues as well including cervix, bladder, colon, and upper GI tract. [unreadable] [unreadable] [unreadable]